Ras exchange factors

Pak et al. (37) reported that prARs binds to the PDZ domain of the cAMP-dependent Ras exchange factor, CNrasGEF, via its C-terminal SKV motif. When cells were cotransfected with prARs and CNrasGEF, Ras was found to... 

A nucleotide exchange factor that activates Ras in response to external cues such as growth factors. Localizes to activated receptors, which contain intrinsic tyrosine kinases, through its interaction with the adaptor protein Grb-2. 

Guanine nucleotide exchange factors other than hSos have also been found to activate Ras, as have other effectors (see Table 8.2). These may interact with unique sequences in the effector loop. The question remains, however, as to how many different effectors can attach to activated Ras and what determines the level of their priority. 

The discovery of PLCs reveals a fourth mechanism whereby the enzyme can be activated (Fig. 20-5). PLCs possesses two Ras-binding (RA) domains in its carboxyl terminal region, and occupancy of these by Ras-GTP results in activation of the enzyme. In addition, the enzyme possesses a CDC-25 domain at its N-terminus, which serves as a guanine nucleotide exchange factor (GEF) for small GTP-binding proteins such as Ras or RaplA. Thus PLCe can not only activate the GDP-bound forms of these small GTP-binding proteins but can also be... 

Guanine nucleotide exchange factors (GEFs) are the immediate activators of Ras. Upon interaction of a GEF with Ras the binding to the nucleotide is... 

RasGEF Guanine nucleotide exchange factor for Ras-like small GTPases E(MF) 5(5) 8(8) IBRD... 

In addition to its influence on protein—protein interactions, phosphorylation also affects protein structure and activity. One case involves a protein termed dematin headpiece (DHP), an actin-binding protein found in a variety of tissues including heart, brain, skeletal muscle, kidney, and lung." DHP is known to interact with Ras-guanine nucleotide exchange factor (Ras-GRF2) and this interaction can modulate MARK pathways, which can link the cytoskeleton and signaling pathways." ... 

Figure 21.7 Control of the activity of Ras by a balance of the activities of guanine nucleotide exchange factor and GTPase. GAP is the abbreviation for GTPase-activating factor and GEF for guanine nucleotide exchange factor. Both are enzymes. Both the activities are controlled by stimuli from various cell surface receptors. Ras oncogenes are present in about 30% of all human tumours.

---